The development of dynamic cardiac single photon emission computed tomography (SPECT) has the potential to be able to process dynamic cardiac gated data and to offer a sensitive measure of ischemia and to characterize viable myocardium with a versatility of imaging the full armamentarium of available cardiac radiopharmaceuticals. Dynamic cardiac SPECT holds forth the potential of acquiring more and likely better diagnostic information than static studies at no additional cost aside from computational processing. The hypothesis is that estimates of pharmacokinetics of radiotracers are more sensitive measures of cardiac disease than visual interpretations of static images. The proposed work will develop methods of processing dynamic cardiac SPECT data of 99mTc-teboroxime and 201Tl in canine models and patients. New algorithms will be developed that reconstruct 3D images of the physiological kinetic model parameters of the heart without artifacts from dynamically acquired tomographic projections. Specifically: 1) Algorithms for reconstructing parametric images either from dynamic reconstructed SPECT data or from cardiac gated projection measurements, 2) Algorithms for automatic segmentation of regions of interest and generation of time activity curves for blood, myocardial, liver, and background tissue, and 3) Algorithms for analysis of effects of SPECT physics and human physiology on the bias and variance of estimated kinetic parameters will be developed, thereby producing a more sensitive measure of ischemic and viable myocardium. The proposed work will develop applied mathematical tools to accurately and precisely quantify kinetic parameters and systematically evaluate these methods with computer simulations, canine experiments, and clinical studies. The goal is to develop methods that use existing single- and multi-detector SPECT systems; and, in so doing, make dynamic SPECT useful even in those clinics which have only single-detector SPECT systems and are thus not able to perform rapid acquisitions. The developed techniques will provide improved health care through better detectability of myocardial infarcts, better diagnosis of ischemic heart disease, and better evaluation of tissue viability without additional costs for the SPECT procedure. Many of the methods developed will also be applicable to imaging the myocardium with other perfusion agents such as NOET, apoptosis agent annexin V, glucose analogues such as 18FDG, and fatty acids such as 123IPPA. Also, these techniques will be applicable to imaging tumors and other organ systems such as kidney and brain.